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In this study, we investigated the involvement of voltage-gated calcium channels (VGCCs) in the differentiation of the F11 cell line, a widely used translational model derived from the fusion of mouse neuroblastoma cells with rat dorsal root ganglion neurons. Differentiation was associated with greater KCl-evoked increases in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and with upregulated expression of VGCC-encoding genes, particularly those for L-type channels. Pharmacological inhibition of L-type VGCCs reduced the KCl-evoked intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    increase and impaired neurite outgrowth, underscoring their role in differentiation. Additionally, overexpression of Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 in non-differentiated F11 cells enhanced neuronal features, including greater KCl-evoked increases in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and neurite outgrowth. However, under differentiation conditions, Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 overexpression disrupted the acquisition of neuronal features and coincided with increased intracellular oxidative stress. Notably, this effect was more pronounced for Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 than for the higher activation-threshold Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 channels. These findings highlight the dual role of L-type VGCCs in neuronal differentiation and oxidative stress regulation, demonstrating that their precise modulation is critical for proper neuronal development. Moreover, the shared molecular pathways between F11 cell differentiation and neurogenesis reinforce the translational value of this model for drug discovery efforts targeting oxidative stress-mediated neuronal dysfunction, such as in neurodegenerative diseases and neuropathic pain.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-44595-1","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:42:20Z","timestamp":1774280540000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Voltage-gated calcium channels as key regulators of neuronal differentiation in the immortalized dorsal root ganglion neuronal cell line F11"],"prefix":"10.1038","volume":"16","author":[{"given":"D.","family":"L\u00f3pez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Brea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Barro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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